Understanding brain cancer and exploiting its vulnerabilities.

Brain cancer is one of the most devastating neoplasms affecting both children and adults. Its dismal prognosis has for long-time discouraged research in this area. However, in the last 10-15 years remarkable progress has been made in our understanding of brain cancer biology, thus showing promise for the identification of new ways to treat these tumors towards the improvement of patients' survival and quality of life.

Author Correction: BCL7A-containing SWI/SNF/BAF complexes modulate mitochondrial bioenergetics during neural progenitor differentiation.

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Gelling Bodies: Understanding the Mechanisms Underlying Arsenic Trioxide Action.

The study by Bercier and colleagues investigates the mechanisms of action of arsenic trioxide (ATO). The authors find that ATO promotes transition of PML nuclear bodies to a gel-like state via the PML trimerization domain and a critical cysteine residue. Overall, this work sheds new light onto how PML-RARα, the oncogene of APL, is targeted by ATO for disease eradication.

(B)On(e)-cohistones and the epigenetic alterations at the root of bone cancer.

Identification of mutations in histones in a number of human neoplasms and developmental syndromes represents the most compelling evidence to date for a causal role of epigenetic perturbations in human disease. In most cases, these mutations have gain of function properties that cause deviation from normal developmental processes leading to embryo defects and/or neoplastic transformation. These exciting discoveries represent a step-change in our understanding of the role of chromatin (dys)regulation in development and disease.

Deep phenotyping and lifetime trajectories reveal limited effects of longevity regulators on the aging process in C57BL/6J mice.

Current concepts regarding the biology of aging are primarily based on studies aimed at identifying factors regulating lifespan. However, lifespan as a sole proxy measure for aging can be of limited value because it may be restricted by specific pathologies. Here, we employ large-scale phenotyping to analyze hundreds of markers in aging male C57BL/6J mice.

BCL7A-containing SWI/SNF/BAF complexes modulate mitochondrial bioenergetics during neural progenitor differentiation.

Mammalian SWI/SNF/BAF chromatin remodeling complexes influence cell lineage determination. While the contribution of these complexes to neural progenitor cell (NPC) proliferation and differentiation has been reported, little is known about the transcriptional profiles that determine neurogenesis or gliogenesis. Here, we report that BCL7A is a modulator of the SWI/SNF/BAF complex that stimulates the genome-wide occupancy of the ATPase subunit BRG1.

Aberrant paracrine signalling for bone remodelling underlies the mutant histone-driven giant cell tumour of bone.

Oncohistones represent compelling evidence for a causative role of epigenetic perturbations in cancer. Giant cell tumours of bone (GCTs) are characterised by a mutated histone H3.3 as the sole genetic driver present in bone-forming osteoprogenitor cells but absent from abnormally large bone-resorbing osteoclasts which represent the hallmark of these neoplasms.

Edge-Based Transfer Learning for Classroom Occupancy Detection in a Smart Campus Context.

Studies and systems that are aimed at the identification of the presence of people within an indoor environment and the monitoring of their activities and flows have been receiving more attention in recent years, specifically since the beginning of the COVID-19 pandemic. This paper proposes an approach for people counting that is based on the use of cameras and Raspberry Pi platforms, together with an edge-based transfer learning framework that is enriched with specific image processing strategies, with the aim of this approach being adopted in different indoor environments without the need for tailored training phases. The system was deployed on a university campus, which was chosen as the case study.

Aberrant chromatin landscape following loss of the H3.3 chaperone Daxx in haematopoietic precursors leads to Pu.1-mediated neutrophilia and inflammation.

Defective silencing of retrotransposable elements has been linked to inflammageing, cancer and autoimmune diseases. However, the underlying mechanisms are only partially understood. Here we implicate the histone H3.

Heterogeneity and excitability of BRAFV600E-induced tumors is determined by Akt/mTOR-signaling state and Trp53-loss.

Background: Developmental brain tumors harboring BRAFV600E somatic mutation are diverse. Here, we describe molecular factors that determine BRAFV600E-induced tumor biology and function.

Methods: Intraventricular in utero electroporation in combination with the piggyBac transposon system was utilized to generate developmental brain neoplasms, which were comprehensively analyzed with regard to growth using near-infrared in-vivo imaging, transcript signatures by RNA sequencing, and neuronal activity by multielectrode arrays.

The histone code in dementia: Transcriptional and chromatin plasticity fades away.

With the aging of the population, Alzheimer's disease and other forms of dementia represent major challenges for health care systems globally. To date, the molecular mechanisms underlying the pathophysiology of dementia remain elusive, with a consequent negative impact in developing efficient disease modifiers. New exciting findings suggest that modulation of the histone code may influence transcriptional networks at the root of neuronal plasticity and cognitive performance.

Alcohol-abuse drug disulfiram targets pediatric glioma via MLL degradation.

Pediatric gliomas comprise a broad range of brain tumors derived from glial cells. While high-grade gliomas are often resistant to therapy and associated with a poor outcome, children with low-grade gliomas face a better prognosis. However, the treatment of low-grade gliomas is often associated with severe long-term adverse effects.

On Supporting University Communities in Indoor Wayfinding: An Inclusive Design Approach.

Mobility can be defined as the ability of people to move, live and interact with the space. In this context, indoor mobility, in terms of indoor localization and wayfinding, is a relevant topic due to the challenges it presents, in comparison with outdoor mobility, where GPS is hardly exploited. Knowing how to move in an indoor environment can be crucial for people with disabilities, and in particular for blind users, but it can provide several advantages also to any person who is moving in an unfamiliar place.

Meclofenamate causes loss of cellular tethering and decoupling of functional networks in glioblastoma.

Background: Glioblastoma cells assemble to a syncytial communicating network based on tumor microtubes (TMs) as ultra-long membrane protrusions. The relationship between network architecture and transcriptional profile remains poorly investigated. Drugs that interfere with this syncytial connectivity such as meclofenamate (MFA) may be highly attractive for glioblastoma therapy.

The Prediction of Body Mass Index from Negative Affectivity through Machine Learning: A Confirmatory Study.

This study investigates on the relationship between affect-related psychological variables and Body Mass Index (BMI). We have utilized a novel method based on machine learning (ML) algorithms that forecast unobserved BMI values based on psychological variables, like depression, as predictors. We have employed various machine learning algorithms, including gradient boosting and random forest, with psychological variables relative to 221 subjects to predict both the BMI values and the BMI status (normal, overweight, and obese) of those subjects.

Histone H3.3G34-Mutant Interneuron Progenitors Co-opt PDGFRA for Gliomagenesis.

Histone H3.3 glycine 34 to arginine/valine (G34R/V) mutations drive deadly gliomas and show exquisite regional and temporal specificity, suggesting a developmental context permissive to their effects. Here we show that 50% of G34R/V tumors (n = 95) bear activating PDGFRA mutations that display strong selection pressure at recurrence.

RaveGuard: A Noise Monitoring Platform Using Low-End Microphones and Machine Learning.

Urban noise is one of the most serious and underestimated environmental problems. According to the World Health Organization, noise pollution from traffic and other human activities, negatively impact the population health and life quality. Monitoring noise usually requires the use of professional and expensive instruments, called phonometers, able to accurately measure sound pressure levels.

Pervasive H3K27 Acetylation Leads to ERV Expression and a Therapeutic Vulnerability in H3K27M Gliomas.

High-grade gliomas defined by histone 3 K27M driver mutations exhibit global loss of H3K27 trimethylation and reciprocal gain of H3K27 acetylation, respectively shaping repressive and active chromatin landscapes. We generated tumor-derived isogenic models bearing this mutation and show that it leads to pervasive H3K27ac deposition across the genome. In turn, active enhancers and promoters are not created de novo and instead reflect the epigenomic landscape of the cell of origin.

H3K27M induces defective chromatin spread of PRC2-mediated repressive H3K27me2/me3 and is essential for glioma tumorigenesis.

Lys-27-Met mutations in histone 3 genes (H3K27M) characterize a subgroup of deadly gliomas and decrease genome-wide H3K27 trimethylation. Here we use primary H3K27M tumor lines and isogenic CRISPR-edited controls to assess H3K27M effects in vitro and in vivo. We find that whereas H3K27me3 and H3K27me2 are normally deposited by PRC2 across broad regions, their deposition is severely reduced in H3.

Elevated signature of a gene module coexpressed with CDC20 marks genomic instability in glioma.

Genomic instability (GI) drives tumor heterogeneity and promotes tumor progression and therapy resistance. However, causative factors underlying GI and means for clinical detection of GI in glioma are inadequately identified. We describe here that elevated expression of a gene module coexpressed with CDC20 (CDC20-M), the activator of the anaphase-promoting complex in the cell cycle, marks GI in glioma.

The SWI/SNF subunit Bcl7a contributes to motor coordination and Purkinje cell function.

Chromatin remodelers have emerged as prominent regulators of epigenetic processes and potential drivers of various human pathologies. The multi-subunit chromatin-remodeling SWI/SNF complex determines gene expression programs and, consequently, contributes to the differentiation, maturation and plasticity of neurons. Here, we investigate the elusive biological function of Bcl7a and Bcl7b, two newly identified subunits of the SWI/SNF complex that are highly expressed throughout the brain.